title: Protective effect of dietary tocotrienols against infection and inflammation-induced hyperlipidemia: an in vivo and in silico study.
abstract: Currently used hypolipidemic drugs, Fluvastatin and Atorvastatin, act via inhibiting the rate-limiting enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase of the mevalonate pathway. The associated severe side-effects of these statins led us to explore the therapeutic potentials of naturally occurring Tocomin (mixture of dietary α-, β-, γ- and δ-tocotrienols). Tocomin (10 mg) was orally administered daily for 10 days before and 12 h after bacterial lipopolysaccharide (200 μg) or 24 h after zymosan (20 mg) or turpentine (0.5 mL) to Syrian hamsters. The data showed that Tocomin significantly reduced the levels of plasma and lipoprotein lipids, cholesterol, apoB, small dense (sd)-LDL as well as LDL in the hyperlipidemia-induced hamsters. Further, the mechanism of action of α-, β-, γ- and δ-tocotrienols was validated by docking studies with HMG-CoA reductase enzyme using the Molegro Virtual Docker. The inhibition of HMG-CoA reductase predicted in terms of MolDockScore and interaction energy suggest the comparative potential in the descending order: Atorvastatin > Fluvastatin ~ δ > γ > β > α. The results favor the daily intake of naturally occurring tocotrienols as dietary supplement in the prevention and treatment of infection/inflammation induced dyslipidemia compared with the hypolipidemic drugs.
authors.affiliation: Department of Biochemistry, J N Medical College, A M University, Aligarh, 202002, India; Department of Biotechnology, Integral University, Lucknow 226026, India. contactskhan@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Salman Khan
authors.forename: Salman
authors.initials: S
authors.lastname: Akhtar
authors.forename: Othman A
authors.initials: OA
authors.lastname: Al-Sagair
authors.forename: Jamal M
authors.initials: JM
authors.lastname: Arif
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy*; D007211:Indoles / Q000494:pharmacology; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D015394:Molecular Structure; D011758:Pyrroles / Q000494:pharmacology; D024508:Tocotrienols / Q000494:pharmacology*
chemical_list: D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008077:Lipoproteins, LDL; D011758:Pyrroles; C570135:Tocomin; D024508:Tocotrienols; D000077340:Fluvastatin; D002784:Cholesterol; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases